Giuseppe Zanni

Menstrual cycle-related changes in plasma oxytocin are relevant to normal sexual function in healthy women

Circulating levels of the neuro-hypophysial nonapeptide oxytocin increase during sexual arousal and orgasm in both men and women. A few studies have evaluated the effect of the menstrual cycle on plasma oxytocin in normally cycling, sexually active, healthy fertile women using or not using contraceptive pills. In 20 ovulating women and 10 women taking an oral contraceptive (group 1 and group 2, respectively), sexual function, hormonal profile, and plasma oxytocin (OT) were evaluated throughout the menstrual cycle. In group 1, plasma OT was significantly lower during the luteal phase in comparison with both the follicular and ovulatory phases. Plasma oxytocin was significantly correlated with the lubrication domain of the Female Sexual Function Index (FSFI) during the luteal phase and showed a trend towards statistical significance during the follicular phase. In group 2, plasma OT did not show any significant fluctuation throughout the menstrual cycle, even though a significant correlation was evident with both the arousal and the lubrication domain of the FSFI during the assumption of the contraceptive pill. These findings suggest that plasma OT fluctuates throughout the menstrual cycle in normally cycling healthy fertile women with adequate sexual activity but not taking any oral contraceptive pill. Moreover, plasma OT levels significantly relates to the genital lubrication in both women taking and not taking oral contraceptive pill apparently confirming its role in peripheral activation of sexual function.

Menstrual Cycle-Related Changes in Circulating Androgens in Healthy Women With Self-Reported Normal Sexual Function

INTRODUCTION There is currently neither a clinically useful, reliable and inexpensive assay to measure circulating levels of free testosterone (T) in the range observed in women, nor is there agreement on the serum free T threshold defining hypoandrogenism that is associated with female-impaired sexual function. AIM Following the Clinical and Laboratory Standards Institute guidelines, we generated clinically applicable ranges for circulating androgens during specific phases of the menstrual cycle in a convenience sample of 120 reproductive-aged, regularly cycling healthy European Caucasian women with self-reported normal sexual function. METHODS All participants were asked to complete a semistructured interview and fill out a set of validated questionnaires, including the Female Sexual Function Index, the Female Sexual Distress Scale, and the 21-item Becks Inventory for Depression. Between 8 am and 10 am, a venous blood sample was drawn from each participant during the midfollicular (day 5 to 8), the ovulatory (day 13 to 15), and the midluteal phase (day 19 to 22) of the same menstrual cycle. MAIN OUTCOME MEASURES Serum levels of total and free testosterone, Delta(4)-androstenedione, dehydroepiandrosterone sulphate and sex hormone-binding globulin during the midfollicular, ovulatory and midluteal phase of the same menstrual cycle. RESULTS Total and free T levels showed significant fluctuations, peaking during the ovulatory phase. No significant variation during the menstrual cycle were observed for Delta(4)-androstenedione and dehydroepiandrosterone sulphate. Despite the careful selection of participants that yielded an homogeneous group of women without sexual disorders, we observed a wide range of distribution for each of the circulating androgens measured in this study. CONCLUSIONS This report provides clinically applicable ranges for androgens throughout the menstrual cycle in reproductive-aged, regularly cycling, young healthy Caucasian European women with self-reported normal sexual function.

Is extended and saturation biopsy necessary

Prostate biopsy (PBx) techniques have significantly changed since the original Hodges ‘sextant scheme’, which should now be considered obsolete. The feasibility of carrying out a biopsy scheme with a high number of cores in an outpatient setting is a result of the great improvement and efficacy of local anesthesia. Peri‐prostatic nerve block with lidocaine injection should be considered the ‘gold standard’ because it provides the best pain relief to patients undergoing PBx. The optimal extended protocol should now include the sextant template with an additional 4–6 cores directed laterally (anterior horn) to the base and medially to the apex. Saturation biopsies (i.e. template with ≥20 cores, including transition zone) should be carried out only when biopsies are repeated in patients where there is a high suspicion of prostate cancer. Complementary imaging methods (such as color‐ and power‐Doppler imaging, with or without contrast enhancement, and elastography) could be used in order to increase the accuracy of biopsy and reduce the number of unnecessary procedures. Nevertheless, the routine use of these methods is still under evaluation.

Remembered International Index of Erectile Function domain scores are not accurate in assessing preoperative potency in candidates for bilateral nerve-sparing radical retropubic prostatectomy

INTRODUCTION The reliability of reported postoperative data in patients undergoing nerve-sparing radical retropubic prostatectomy is often limited because the degree of sexual function (SF) has not been assessed objectively both before and after treatment. Most reports include only a retrospective chart review, and there is a question of whether such data are accurate. AIM To test the agreement between a remembered International Index of Erectile Function (IIEF) score, which targeted SF regarding a period preceding the surgery by 6 months and a real-time IIEF, 4 weeks prior to surgery, in candidates for bilateral nerve-sparing radical retropubic prostatectomy (BNSRRP). METHODS From May 2005 to May 2006, 333 consecutive patients were candidates for BNSRRP at our institution. Upon admission on the day prior to surgery, each patient was asked to complete a set of validated questionnaires including both a remembered and a real-time IIEF. Two-tailed Students t-test, chi2 test, Pearson correlation coefficient, multivariate regression analyses, and interrater agreement (kappa) were used to test the agreement between the two assessments. MAIN OUTCOME MEASURES Assessing the preoperative SF characteristics of candidates for a BNSRRP, and testing the reliability of a remembered IIEF with the interrater agreement (kappa) test. RESULTS Mean scores for the remembered IIEF were overall better than the real-time IIEF scores, as supported by direct comparison of the mean IIEF domain scores. Univariate correlation analysis and multivariate regression analysis indicated a significant correlation in the quality of the SF during the two periods. However, the remembered IIEF scores did not show a good statistical agreement with those of the real-time assessment, as demonstrated by the interrater agreement analysis. CONCLUSIONS Because of the lack of significant agreement between remembered and real-time IIEF scores, the present findings indicate that remembered IIEF should not be used to assess SF in a real-life clinical setting in candidates for BNSRRP.

Clinical update on phosphodiesterase type-5 inhibitors for erectile dysfunction

Erectile dysfunction (ED) affects the sexual lives of millions of men. The first-line oral pharmacotherapy for most ED patients is phosphodiesterase type-5 (PDE-5) inhibitors, of which three are available. Sildenafil is the most widely prescribed oral agent for ED and has a very satisfactory efficacy–safety profile in all patient categories. Tadalafil and vardenafil were introduced in the European Union and in the United States in 2003 and 2004, respectively. The three PDE-5 inhibitors share many pharmacological and clinical characteristics, and each has unique features. This review, which is based on the contemporary literature on PDE-5 inhibitors, describes the chemical, pharmacological, and clinical features of sildenafil, vardenafil, and tadalafil. The first section reviews the pathophysiology of penile erection and PDE-5 inhibitor pharmacology. The second section summarizes data regarding efficacy and safety of the three drugs in treating ED in the general population as well as in selected patient categories.

Holmium laser enucleation of the prostate and holmium laser ablation of the prostate: indications and outcome.

Purpose of review Holmium laser enucleation of the prostate (HoLEP) has been proposed as an alternative to transurethral resection of the prostate and to open prostatectomy for patients with lower urinary tract symptoms because of large benign prostatic enlargement. The aim of this review is to critically analyze currently available evidence-based reports regarding HoLEP, with particular interest in long-term follow-up results. Recent findings The use of holmium laser for the treatment of benign prostatic hyperplasia was first reported in 1996. HoLEP seems to represent a valid alternative to both transurethral resection of the prostate and open prostatectomy, with valid long-term functional results, a low rate of short-term and long-term complications, and very low rates of reintervention. Summary HoLEP represents a valid alternative to both transurethral resection of the prostate and open prostatectomy for treatment of patients suffering from lower urinary tract symptoms due to benign prostatic enlargement. The recently published long-term follow-up data demonstrate the durability of functional results. HoLEP can be offered as the size-independent gold standard treatment of patients with lower urinary tract symptoms because of benign prostatic enlargement.

ORIGINAL RESEARCH—EJACULATORY DISORDERS: Quantitative Sensory Testing of Peripheral Thresholds in Patients with Lifelong Premature Ejaculation: A Case-Controlled Study

INTRODUCTION The main functional factors related to lifelong premature ejaculation (PE) etiology have been suggested to be penile hypersensitivity, greater cortical penile representation, and disturbance of central serotoninergic neurotransmission. AIMS To quantitatively assess penile sensory thresholds in European Caucasian patients with lifelong PE using the Genito-Sensory Analyzer (GSA, Medoc, Ramat Yishai, Israel) as compared with those of an age-comparable sample of volunteers without any ejaculatory compliant. METHODS Forty-two consecutive right-handed, fully potent patients with lifelong PE and 41 right-handed, fully potent, age-comparable volunteers with normal ejaculatory function were enrolled. Each man was assessed via comprehensive medical and sexual history; detailed physical examination; subjective scoring of sexual symptoms with the International Index of Erectile Function; and four consecutive measurements of intravaginal ejaculatory latency time with the stopwatch method. All men completed a detailed genital sensory evaluation using the GSA; thermal and vibratory sensation thresholds were computed at the pulp of the right index finger, and lateral aspect of penile shaft and glans, bilaterally. MAIN OUTCOME MEASURES Comparing quantitatively assessed penile thermal and vibratory sensory thresholds between men with lifelong PE and controls without any ejaculatory compliant. RESULTS Patients showed significantly higher (P < 0.001) thresholds at the right index finger but similar penile and glans thresholds for warm sensation as compared with controls. Cold sensation thresholds were not significantly different between groups at the right index finger or penile shaft, but glans thresholds for cold sensation were bilaterally significantly lower (P = 0.01) in patients. Patients showed significantly higher (all P < or = 0.04) vibratory sensation thresholds for right index finger, penile shaft, and glans, bilaterally, as compared with controls. CONCLUSIONS Quantitative sensory testing analysis suggests that patients with lifelong PE might have a hypo- rather than hypersensitivity profile in terms of peripheral sensory thresholds. The peripheral neuropathophysiology of lifelong PE remains to be clarified.

Postoperative Orgasmic Function Increases over Time in Patients Undergoing Nerve‐Sparing Radical Prostatectomy

INTRODUCTION Postprostatectomy orgasmic function (OF) remains poorly defined. AIMS To assess OF over time in patients who underwent bilateral nerve-sparing radical retropubic prostatectomy (BNSRRP) for organ-confined prostate cancer (PCa). METHODS Baseline data were obtained from 334 consecutive preoperatively sexually active PCa patients at hospital admission; data included a medical and sexual history, IIEF domain scores, and ICIQ-SF. Questionnaire were then completed every 12 months postoperatively, and patients participated in a semistructured interview at the 12-month (191/334 [57.2%] patients), 24-month (95/334 [28.4%] patients), 36-month (42/334 [12.6%] patients), and 48-month (19/334 [5.7%] patients) follow-up (FU). MAIN OUTCOME MEASURES IIEF-OF domain values throughout the FU. Multivariate linear regression analysis (MVA) of the association between predictors (patients age, IIEF-erectile function [EF], ICIQ-SF, and the use of postoperative proerectile pharmacological treatments) and the IIEF-OF at 12-month, 24-month, and 36-month FU. RESULTS Preoperative mean (median) IIEF-OF was 7.6 (10). The anova analysis showed an increase of the IIEF-OF values (P = 0.008; F = 4.009) throughout the FU (namely, IIEF-OF 12-month: 6.1 [6]; 24-month: 7.2 [8]; 36-month: 7.3 [8]; and 48-month: 7.7 [9.50]). The 12-month MVA showed that while proerectile oral therapy did not affect postoperative OF (P = 0.150; Beta 0.081), IIEF-OF linearly increased with IIEF-EF (P < 0.001; Beta 0.425). Conversely, IIEF-OF linearly decreased with patients age (P < 0.001; Beta -0.135) and with ICQ-SF scores (P < 0.001; Beta -0.438). The 24-month and 36-month analyses showed that IIEF-OF still linearly increased with IIEF-EF (P < 0.001; Beta 0.540, and P < 0.001; Beta 0.536 respectively at the 24- and 36-month FU), whereas pharmacological therapy, rate of urinary continence, and patients age did not significantly affect postoperative OF. CONCLUSIONS Postoperative OF significantly ameliorates over time in patients undergoing BNSRRP. The higher the postoperative EF score, the higher the OF throughout the FU time frame.

Sex Hormone-binding Globulin: A Novel Marker for Nodal Metastases Prediction in Prostate Cancer Patients Undergoing Extended Pelvic Lymph Node Dissection

OBJECTIVES To examine the association between sex hormone-binding globulin (SHBG) and lymph node invasion (LNI) in patients treated with radical retropubic prostatectomy and extended pelvic lymph node dissection (ePLND). METHODS The preoperative serum SHBG level was measured in a cohort of 168 consecutive patients (mean age 63.9 years, range 48-77) who underwent radical retropubic prostatectomy with ePLND for clinically localized prostate cancer. Logistic regression models tested the association between the predictors (including prostate-specific antigen, clinical stage, primary and secondary biopsy Gleason grades, and SHBG) and LNI. Logistic regression coefficients were used to calculate the predictive accuracy, which was subjected to 200 bootstrap resamples to reduce overfit bias. RESULTS Thirteen patients (7.7%) had LNI. The mean serum SHBG level was significantly greater in the patients with LNI than in those without LNI (50.0 vs 35.1 nmol/L, respectively; P < .001). Univariate analysis indicated that preoperative SHBG was the single most informative predictor of LNI (77.8% vs 71.7% for prostate-specific antigen, 63.9% for clinical stage, and 63.1% and 54.2% for primary and secondary Gleason grade, respectively). On multivariate analysis, preoperative SHBG was still significantly associated with LNI (P < .001), after accounting for the other variables. The addition of preoperative SHBG increased the predictive accuracy of the base model using clinically established predictors from 72.7% to 82.8% (10.1% gain; P < .001). CONCLUSIONS The results of this study provide novel evidence that SHBG might serve as a significant multivariate predictor of LNI in patients with prostate cancer undergoing ePLND. The use of preoperative serum SHBG could help to identify patients at risk of LNI who should undergo ePLND.

The role of the urologist in the management of female sexual dysfunctions.

Purpose of review The present minireview is aimed at investigating the association between female sexual dysfunction and urinary incontinence or lower urinary tract symptoms, two of the most frequently encountered urological disorders. Recent findings Sexual dysfunction in women is a multifactorial and multidimensional condition combining several biological, psychological, medical, interpersonal and social components. According to the National Health and Social Life Survey, approximately 43% of American women suffer from sexual disorders. There have been few investigations about the prevalence and predictors of female sexual function or sexual dysfunction across Europe. Based on everyday clinical practice and according to the most recent peer-reviewed publications, there is a critical correlation between urogynaecological conditions and womens sexual disorders. Interestingly, an increasing number of papers have raised the issue of womens sexual function in patients who have undergone urogynaecological radical pelvic surgery for urological malignancies. The role of the urologist in treating the couple covers the third part of this paper, and attempts to show the significant correlation between the presence of any female sexual dysfunction and so-called patient-partner satisfaction. Summary This minireview underlines the significant role of the urologist in the management of female sexual dysfunctions, mainly in women with urogynaecological disorders. Evaluation by the patients partner and its impact on urological patients has also been stressed.